Identification of RP11‐770J1.4 as immune‐related lncRNA regulating the CTXN1–cGAS–STING axis in histologically lower‐grade glioma
Abstract Human gliomas are lethal brain cancers. Emerging evidence revealed the regulatory role of long noncoding RNAs (lncRNAs) in tumors. Here, we performed a comprehensive analysis of the expression profiles of RNAs in histologically lower‐grade glioma (LGG). Enrichment analysis revealed that gli...
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| Format: | Article |
| Language: | English |
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Wiley
2023-12-01
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| Series: | MedComm |
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| Online Access: | https://doi.org/10.1002/mco2.458 |
| _version_ | 1797373522649022464 |
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| author | Qiyuan Zhuang Chaxian Liu Yihan Hu Ying Liu Yingying Lyu Yuheng Liao Liang Chen Hui Yang Ying Mao |
| author_facet | Qiyuan Zhuang Chaxian Liu Yihan Hu Ying Liu Yingying Lyu Yuheng Liao Liang Chen Hui Yang Ying Mao |
| author_sort | Qiyuan Zhuang |
| collection | DOAJ |
| description | Abstract Human gliomas are lethal brain cancers. Emerging evidence revealed the regulatory role of long noncoding RNAs (lncRNAs) in tumors. Here, we performed a comprehensive analysis of the expression profiles of RNAs in histologically lower‐grade glioma (LGG). Enrichment analysis revealed that glioma is influenced by immune‐related signatures. Survival analysis further established the close correlation between network features and glioma prognosis. Subsequent experiments showed lncRNA RP11‐770J1.4 regulates CTXN1 expression through hsa‐miR‐124‐3p. Correlation analysis identified lncRNA RP11‐770J1.4 was immune related, specifically involved in the cytosolic DNA sensing pathway. Downregulated lncRNA RP11‐770J1.4 resulted in increased spontaneous gene expression of the cGAS–STING pathway. Single‐cell RNA sequencing analysis, along with investigations in a glioblastoma stem cell model and patient sample analysis, demonstrated the predominant localization of CTXN1 within tumor cores rather than peripheral regions. Immunohistochemistry staining established a negative correlation between CTXN1 expression and infiltration of CD8+ T cells. In vivo, Ctxn1 knockdown in GL261 cells led to decreased tumor burden and improved survival while increasing infiltration of CD8+ T cells. These findings unveil novel insights into the lncRNA RP11‐770J1.4–CTXN1 as a potential immune regulatory axis, highlighting its therapeutic implications for histologically LGGs. |
| first_indexed | 2024-03-08T18:51:43Z |
| format | Article |
| id | doaj.art-1f8cc3e629de40b28264854ac5a191c1 |
| institution | Directory Open Access Journal |
| issn | 2688-2663 |
| language | English |
| last_indexed | 2024-03-08T18:51:43Z |
| publishDate | 2023-12-01 |
| publisher | Wiley |
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| series | MedComm |
| spelling | doaj.art-1f8cc3e629de40b28264854ac5a191c12023-12-28T16:52:34ZengWileyMedComm2688-26632023-12-0146n/an/a10.1002/mco2.458Identification of RP11‐770J1.4 as immune‐related lncRNA regulating the CTXN1–cGAS–STING axis in histologically lower‐grade gliomaQiyuan Zhuang0Chaxian Liu1Yihan Hu2Ying Liu3Yingying Lyu4Yuheng Liao5Liang Chen6Hui Yang7Ying Mao8Department of Neurosurgery Huashan Hospital, Fudan University Shanghai ChinaDepartment of Neurosurgery Huashan Hospital, Fudan University Shanghai ChinaSchool of Life Sciences, Fudan University Shanghai ChinaDepartment of Pathology School of Basic Medical Sciences, Fudan University Shanghai ChinaDepartment of Neurosurgery Huashan Hospital, Fudan University Shanghai ChinaKey Laboratory of Medical Epigenetics and Metabolism and Molecular and Cell Biology Lab Institute of Biomedical Sciences, Shanghai Medical College, Fudan University Shanghai ChinaDepartment of Neurosurgery Huashan Hospital, Fudan University Shanghai ChinaDepartment of Neurosurgery Huashan Hospital, Fudan University Shanghai ChinaDepartment of Neurosurgery Huashan Hospital, Fudan University Shanghai ChinaAbstract Human gliomas are lethal brain cancers. Emerging evidence revealed the regulatory role of long noncoding RNAs (lncRNAs) in tumors. Here, we performed a comprehensive analysis of the expression profiles of RNAs in histologically lower‐grade glioma (LGG). Enrichment analysis revealed that glioma is influenced by immune‐related signatures. Survival analysis further established the close correlation between network features and glioma prognosis. Subsequent experiments showed lncRNA RP11‐770J1.4 regulates CTXN1 expression through hsa‐miR‐124‐3p. Correlation analysis identified lncRNA RP11‐770J1.4 was immune related, specifically involved in the cytosolic DNA sensing pathway. Downregulated lncRNA RP11‐770J1.4 resulted in increased spontaneous gene expression of the cGAS–STING pathway. Single‐cell RNA sequencing analysis, along with investigations in a glioblastoma stem cell model and patient sample analysis, demonstrated the predominant localization of CTXN1 within tumor cores rather than peripheral regions. Immunohistochemistry staining established a negative correlation between CTXN1 expression and infiltration of CD8+ T cells. In vivo, Ctxn1 knockdown in GL261 cells led to decreased tumor burden and improved survival while increasing infiltration of CD8+ T cells. These findings unveil novel insights into the lncRNA RP11‐770J1.4–CTXN1 as a potential immune regulatory axis, highlighting its therapeutic implications for histologically LGGs.https://doi.org/10.1002/mco2.458ceRNA networkcytosolic DNA sensing pathwayimmune‐related lncRNAlower‐grade gliomasingle‐cell RNA sequencing |
| spellingShingle | Qiyuan Zhuang Chaxian Liu Yihan Hu Ying Liu Yingying Lyu Yuheng Liao Liang Chen Hui Yang Ying Mao Identification of RP11‐770J1.4 as immune‐related lncRNA regulating the CTXN1–cGAS–STING axis in histologically lower‐grade glioma MedComm ceRNA network cytosolic DNA sensing pathway immune‐related lncRNA lower‐grade glioma single‐cell RNA sequencing |
| title | Identification of RP11‐770J1.4 as immune‐related lncRNA regulating the CTXN1–cGAS–STING axis in histologically lower‐grade glioma |
| title_full | Identification of RP11‐770J1.4 as immune‐related lncRNA regulating the CTXN1–cGAS–STING axis in histologically lower‐grade glioma |
| title_fullStr | Identification of RP11‐770J1.4 as immune‐related lncRNA regulating the CTXN1–cGAS–STING axis in histologically lower‐grade glioma |
| title_full_unstemmed | Identification of RP11‐770J1.4 as immune‐related lncRNA regulating the CTXN1–cGAS–STING axis in histologically lower‐grade glioma |
| title_short | Identification of RP11‐770J1.4 as immune‐related lncRNA regulating the CTXN1–cGAS–STING axis in histologically lower‐grade glioma |
| title_sort | identification of rp11 770j1 4 as immune related lncrna regulating the ctxn1 cgas sting axis in histologically lower grade glioma |
| topic | ceRNA network cytosolic DNA sensing pathway immune‐related lncRNA lower‐grade glioma single‐cell RNA sequencing |
| url | https://doi.org/10.1002/mco2.458 |
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